Art of concentrating pharmaceutical and other liquids



June 27, 1950 R, A, B|ERW|RTH D 2,512,604

ART 0F CQNCENTRATING PHARMACEUTICAL AND OTHER LIQUIDS Filed oct. s, 1944 ff w 29a' 070k i "writ i aum-'7' /NTHKF i 7' 7' ORNE-y tPatented June 27, 1950 ART F CONCENTRATING PHARMACEUTI- CAL AND GTHEB LIQUIDS Rudolph A. Bierwirth, Princeton,

N. J., assignor to Radio Corporation of America, a corporation oi' Delaware Application October 3, 1944, Serial No. 557,053 4 Claims. (Cl. 159-6) This invention relates to the concentration and desiccation by evaporation or distillation of liquids containing animal, vegetable or mineral matter in solution, and has special reference to the art of dehydrating fluent matter of the type which effervesces or foams when subjected to heat or to a vacuum.

While the prior art is replete with so-called save-all systems for preventing the less volatile constitutents of various ebullient liquids from being carried away in the foam or bubbles which are created when such liquids are subjected to heat or to a vacuum, an examination of such systems reveals that they are designed primarily to handle bulk quantities of liquid and are entirely unsuited for use in the dehydration or desiccation of bottled or packaged goods such, for

example, as biological and pharmaceutical products. Thus, while it' is common practice (see U. S. Patent No. 1,202,969) to provide a steam or hot water coil adjacent to the top of a still or other relatively large retort for the purpose olbursting the bubbles which emanate from the material being distilled, it would obviously be impractical to provide each of a, large number of bottles or drug ampoules with such a save-all coil. Similarly, the use of rotating wires for breaking the bubbles (see U. S. Patent No. 1,250,427) would entaila formidable duplication of parts where a large number of containers are to be handled simultaneously. Nor does the addition of anti-foaming chemicals to the liquid (see U. S. Patent No. 1,440,973) or the use of goose-neck containers`v (see U. S. Patent No. 1,475,314) afford a satisfactory solution of the problem, since such means are barred in many cases either by the very nature of the material to be treated or because their use gives rise to other and complex problems of sanitation and Y packaging.

Accordingly, the principal object of the present invention is to provide an improved and rapid method of concentrating or desiccating liquids and other fluent matter, and one which lends itself readily to the processing of drugs and other bottled or packaged goods, in situ.

Another and important object of the invention is to provide an improved dehydrator of the type wherein the material is subjected to radio frequency energy, and one incorporating a highly eiiicient applicator or coupling system for subjccting numerous discrete containers or articles simultaneously and uniformly to the R.F. energy.

Stated brieily: the foregoing and other objects are achieved in accordance with the invention by subjecting the liquid contents of an bottle, test-tube or other open-topped receptacle to a force (e. g., heat and/or a vacuum which produces molecular agitation in the liquid) of an intensity normally suilicient to cause the liquid to give off both gaseous and liquid emanations, and then rotating said receptacle about its vertical axis at a, rate sufficiently rapid to prevent the generation of bubbles or other inflated or deflated liquidillms which might be carried away with the gaseous emanations or vapor. When the receptacle is rotated at the indicated speed the liquid is spread by centrifugal force in a. uniformly thin layer over the inner wall of the receptacle. This speeds up the dehydration process since the liquid now presents a greatly enlarged surface area to the ambient and to the electrodes or other source of energy. The invention may also be said to reside over-sized in the means and in the procedure hereinafter described for applying the foregoing principle to the processing of the tainers simultaneously.

In the drawing Figure 1 is a top plan view, with the cover removed, and Figure 2 is a sectional elevation taken on the line lI-II of Fig. 1, showing an evacuable dehydrator or ampoule drier which is constructed in accordance with the principle of the invention. Figure 3 is a sectional elevational view of another and simplied embodiment of the invention.

In Figs. 1 and 2 the invention is shown embodied in a so-called ampoule drier comprising an evacuable metal cabinet or chamber I containing a number (in this case, twenty-eight) of discrete ampoules or open-topped bottles 3 which are mounted in spaced circumferential array, each upon its own dielectric holder 4 and spindle 5, in the space between two concentrically arranged cylindrical electrodes 'I and 9 The inner electrode 'l is connected to a ground terminal II through a. metal supporting structure I3 .on the base I5 of the cabinet, and the outer electrode 9 is connected to al terminal I7 which extends through an insulating grommet I 9 in the side Wall of the cabinet Each of the rotatable spindles 5 is provided with a gear 2l and these gears are coupled (as by friction) in driven relation with a common motor-driven gear or wheel 23 which is supported for rotation upon a shaft 25 which extends through a vacuum-tight bushing 2l in the base of the cabinet. The cabinet or chamber I is provided with an air-tight cover 4or lid 29 and there is a port 3| adjacent to the base I5 through which a, connection 33 is made contents of numerous conto a water-cooled condenser 35 and vacuum pump (not shown).

The degree of vacuum established in the chamber I, the frequency and intensity of the electrical energy applied to the electrodes 1 and 9, and indeed the size and the speed of rotation of the ampoules or bottles 3 will ordinarily be chosen plates la and 9a respectively, mounted with their concave surfaces presented in capacitive relation with a careful regard to the nature and the quantity of the drug or other ebullient liquid to bc processed. It would obviously be impossible to correlate all of these factors in a single formula applicable to all materials. However, there are certain general rules which are applicable in most cases. Thus, it may be said, generally, that the glass or other dielectric containers 3 must be considerably larger than the original volume of liquid contained therein and that their speed of rotation should be sufficiently rapid to spread the liquid in a relatively thin layer over the inner side walls of the said receptacles without causing it to spill over. Furthermore, the electrodes 1 and 9 should extend well above the normal level of the liquid within the containers 3 andshould preferably extend as far as the highest level reached by the liquid while it is subject to centrifugal force. The centrifugal force applied to the liquid may be of the order of 100 X gravity.

In applying the invention to the desiccation of a liquor containing the drug penicillin in dosy age quantities (in this case 100,000 Oxford units) ,each serving comprised about 1 cubic centimeter of liquor and was contained in an oversized bottle of 20 cubic centimeters capacity. A pressure of about centimeters of mercury was-established in the chamber I and the receptacles were rotated at a speed of 3000 revolutions per minute, for about 3 minutes, while the electrical energy applied to the electrodes 1 and 9 was supplied at an average rate of watts by an oscillator operating at the convenient frequency of 30 megacycles per second. This operation reduced the moisture content to about 4%. The desiccation was completed in a conventional vacuum drying ovenusing a pressure of about 5 millimeters of mercury and a plate temperature of 65 C. In one hour the moisture content was reduced to 0.6%. As claimed in copending joint application of George H. Brown and Rudolph A. Bierwirth, Serial No. 649,296, when a thin fluid film of penicillin liquor is dried rapidly, in the manner above described, to a point whereat its liquid content comprises no less than 5 percent by weight, the ultimate product comprises the amorphous form of penicillin, whereas if the said process is continued to a point whereat the liquid content of the film comprises not more than substantially 5 percent, by weight, the crystalline form of the drug is achieved.

In carrying the invention into effect it is pref- -erable to employ bottles `or ampoules made from glass tubing rather than ordinary cast or blown glass receptacles since the inner surface of the latter type of receptacle may contain irregularities which prevent the liquid `from spreading evenly thereover. Ordinarily, a bottle type receptacle similar to those shown in the drawing is to be preferred to the test-tube or ampoule type, since the reduced neck portion of the bottle forms a positive barrier to the escape of the liquid and permits the use of a receptacle of somewhat smaller size for a given quantity of liquid. When, as shown in Fig. 3, the vacuum chamber is designed to accommodate but a single receptacle the electrodes may comprise a pair of curved across an intervening space to the convex or cylindrical outer surface of the receptacle. In this case the evacuable chamber, here designated la, is provided with a cover 29a constituted of insulating material and the leads Ila and Ha for the electrodes 1a and 9a are supported on the lid.

In conclusion. attention is called to the fact that because the liquid is spread in the form of a relatively thin cylinder, it is possible to couple to it much more readilyv than if it were settled in a solid mass at the bottom of the bottle. Because of this improved coupling. it is possible to use a much lower oscillator frequency (e. g., 30 megacycles as compared to say, 150 megacycles) than had previously been planned for bottlc drying.

It will now be apparent that the present invention provides an improved and rapid method of and apparatus for concentrating or desiccating liquids and other fluent matter, and that the invention lends itself readily to the processing of drugs and other bottled or packaged goods.

What is claimed is:

1. Apparatus for the treatment of liquid matter with an electric field comprising a cylindrical inner conductor presented across an intervening space to the interior of a cylindrical outer conductor, and a plurality of means arranged in circular array between said cylindrical conductors for supporting a' plurality of liquid receptacles for rotation about their vertical axes in said space.

ing said material to centrifugal force of an intensity sufficient to prevent the liberation of said liquid emanations while confining said material to the interior of said receptacle and then removing said gaseous emanations from said receptacle.

4. Method in accordance with claim 3 and wherein the centrifugal force applied to said material is of the order of gravity.

' RUDOLPH A. BIERWIRTH.

REFERENCES CITED The following references are of record in the le of this patent:

UNITED STATES PATENTS Number Name Date Re. 22,322 Goodridge May 25, 1943 931,663 Wilbur Aug. 17, 1909 1,945,867 Rawls Feb. 6, 1934 1,998,332 Page Apr. 16, 1935 2,167,718 Harris et al Aug. 1, 1939 2,167,881 Eberts Aug. 1, 1939 2,234,166 Hickman Mar. 1l, 1941 2,308,008 Hickman Jan. 12, 1943 2,343,667 Hickman Mar. 7, 1944 2,355,887 Moule Aug. 15, 1944 2,385,567 Descarsin Sept. 25, 1945 FOREIGN PATENTS Number Country Date 518,691 Great Britain Mar. 5, 1940 

